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Background. Personalized therapy is becoming increasingly popular in oncological scenarios, not only based on molecular pharmacological targets, but also preventing any drug–drug–gene interaction (DDGI), which could lead to severe toxicities. Single nucleotide polymorphisms (SNPs), the individual germline sequence variations in genes involved in drug metabolism, are correlated to interindividual response to drugs and explain both efficacy and toxicity profiles reported by patients. Case presentation. We present the case of a woman suffering from triple-positive breast cancer; she had early-stage disease at the onset and after four years developed metastatic disease. During her history, she presented different toxicities due to antineoplastic treatments. Particularly, hypertransaminasemia was found during every line of treatment. Nevertheless, we were able to guarantee the patient an excellent therapeutic adhesion thanks to the supportive treatments and the reduction of drug dosage. Moreover, we conducted a simultaneous analysis of the patient’s biochemical and genomic data thanks to Drug-PIN software, and we found several significant SNPs of the main enzymes and transporters involved in drug metabolism. Conclusion. Our case report demonstrated the relevance of DDGI in clinical practice management of a patient treated for advanced breast cancer, suggesting the role of Drug-PIN software as an easy-to-use tool to prevent adverse events during cancer treatment and to help physicians in therapeutic algorithms. However, further studies are needed to confirm these results.

Background Electrochemotherapy (ECT) is a minimally invasive and safe treatment gaining positive and long-lasting antitumoral results that are receiving the attention of the scientific community. It is a local treatment that combines the use of electroporation and the administration of cytotoxic drugs to induce cell death in the target tissue. ECT is largely used for the treatment of cutaneous and subcutaneous lesions, and good results have been reported for the treatment of deep visceral tumors. The latest literature review is provided. Moreover, in line with its development for the treatment of visceral tumors in this article, we describe a novel approach of ECT: endoscopic treatment of colorectal cancer. Endoscopic ECT application was combined with systemic chemotherapy in the treatment of obstructing rectal cancer without prospective surgery. A good response after ECT was described: concentric involvement of the rectum was reduced, and no stenosing lesions were detected. Conclusions Clinical studies have demonstrated that ECT is a very effective treatment for tumors of different histologic types and localizations. Endoscopic treatment for gastrointestinal cancer is an innovative application of ECT. The combination of systemic treatment and ECT was safe and highly effective in the treatment of colorectal cancer, especially when obstructive, giving the patient a significant gain in quality of life.

714 Background: Intermediate IMDC group is the largest and most heterogeneous group of mRCC. Current first-line (1L) therapy options for these patients (pts) are based on either an anti-angiogenic agent (VEGFR-TKI) combined with immunotherapy (IO), or a combo of IO (ipilimumab+nivolumab [I/N]). No biomarkers (BM) for selecting the most effective regimen have been identified so far. Methods: Immunohistochemical expression of PBRM1, PD-L1, CD31, and CD4/CD8 ratio was evaluated on histological samples of intermediate-risk mRCC pts treated with VEGFR-TKI monotherapy, and then in pts receiving a VEGFR-TKI-based therapy or the immune doublet I/N. PBRM1 positivity score was based on the percentage of positive cells and on the intensity of nuclear expression; PD-L1 positivity was defined as CPS≥10; CD31 high-density had moderate to strong nuclear staining; and the CD4/CD8 ratio cut-off for positivity was >0.2. Cox model was used to assess the correlation between BM and outcomes; PFS and OS were estimated by Kaplan-Meier method. Results: After screening of tumor tissues from 150 pts, a total of 111 were included in the final analysis (Table). In pts treated with VEGFR-TKI monotherapy, a significant correlation with PFS was observed with loss of PBRM1 expression (HR 0.58, p=0.035), PD-L1 negativity (HR 0.44, p=0.048), and high CD4/CD8 ratio (HR 0.62, p=0.073). CD31 density did not significantly correlate with PFS. A profile potentially predictive of angiogenesis (AP+) was defined based on the PBRM1 loss, PD-L1 negative, and high CD4/CD8. In pts treated with VEGFR-TKI monotherapy, tumors with the AP+ (43% of all cases) had a significantly longer median PFS (mPFS 23.8 vs. 11.8 months, p=0.003) and mOS (41.5 vs. 26.9 months, p=0.024) compared to the others. The AP+ retained its significant correlation with PFS (mPFS 23.8 vs. 11.1 months, p

Drug&ndash, drug interactions (DDIs) can affect both treatment efficacy and toxicity. We used Drug-PIN&reg, (Personalized Interactions Network) software in colorectal cancer (CRC) patients to evaluate drug&ndash, drug&ndash, gene interactions (DDGIs), defined as the combination of DDIs and individual genetic polymorphisms. Inclusion criteria were: (i) stage II-IV CRC, (ii) ECOG PS (Performance status sec. Eastern coperative oncology group) &le, 2, (iii) &ge, 5 concomitant drugs, and (iv) adequate renal, hepatic, and bone marrow function. The Drug-PIN&reg, system analyzes interactions between active and/or pro-drug forms by integrating biochemical, demographic, and genomic data from 110 SNPs. We selected DDI, DrugPin1, and DrugPin2 scores, resulting from concomitant medication interactions, concomitant medications, and SNP profiles, and DrugPin1 added to chemotherapy drugs, respectively. Thirty-four patients, taking a median of seven concomitant medications, were included. The median DrugPin1 and DrugPin2 scores were 42.6 and 77.7, respectively. In 13 patients, the DrugPin2 score was two-fold higher than the DrugPin1 score, with 7 (54%) of these patients experiencing severe toxicity that required hospitalization. On chi-squared testing for any toxicity, a doubled DrugPin2 score (p = 0.001) was significantly related to G3&ndash, G4 toxicity. Drug-PIN&reg, software may prevent severe adverse events, decrease hospitalizations, and improve survival in cancer patients.

Background: Perivascular epithelioid cell tumours (PEComas) are mesenchymal neoplasms with variable biological behaviour, ranging from benign to extremely aggressive diseases able to metastasize. No prospective studies are available to define a validate approach to this type of tumours. Case presentation: We present a case report of a 53-year-old woman affected by advanced retroperitoneal PEComa who developed an abdominal disease progression after 40 months of therapy with mTOR inhibitor. The patient underwent cyto-reductive surgery followed by radiotherapy on the residual disease and started chemotherapy with olaratumab plus doxorubicin for seven cycles achieving a partial response so she continued monotherapy with olaratumab for one year with stable disease to quarterly CT evaluation. On September 2019 treatment was definitely interrupted because of marketing authorisation of olaratumab was revoked due to insufficient proof of its medical advantage in phase III trial ANNOUNCE. Currently the patient is still in follow up after 18 months from the interruption of therapy, without a disease progression. Discussion and Conclusion: In our PEComa clinical case, we highlight how a multidisciplinary approach can lead to disease control and a long clinical benefit.

Drug–drug interactions (DDIs) can affect both treatment efficacy and toxicity. We used Drug-PIN® (Personalized Interactions Network) software in colorectal cancer (CRC) patients to evaluate drug–drug–gene interactions (DDGIs), defined as the combination of DDIs and individual genetic polymorphisms. Inclusion criteria were: (i) stage II-IV CRC; (ii) ECOG PS (Performance status sec. Eastern coperative oncology group) ≤2; (iii) ≥5 concomitant drugs; and (iv) adequate renal, hepatic, and bone marrow function. The Drug-PIN® system analyzes interactions between active and/or pro-drug forms by integrating biochemical, demographic, and genomic data from 110 SNPs. We selected DDI, DrugPin1, and DrugPin2 scores, resulting from concomitant medication interactions, concomitant medications, and SNP profiles, and DrugPin1 added to chemotherapy drugs, respectively. Thirty-four patients, taking a median of seven concomitant medications, were included. The median DrugPin1 and DrugPin2 scores were 42.6 and 77.7, respectively. In 13 patients, the DrugPin2 score was two-fold higher than the DrugPin1 score, with 7 (54%) of these patients experiencing severe toxicity that required hospitalization. On chi-squared testing for any toxicity, a doubled DrugPin2 score (p = 0.001) was significantly related to G3–G4 toxicity. Drug-PIN® software may prevent severe adverse events, decrease hospitalizations, and improve survival in cancer patients.

Melanoma onset and progression are associated with a high variety of activating mutations in the MAPK-pathway, most frequently involving BRAF (35-45%) and NRAS (15-25%) genes, but also c-KIT and PTEN. Targeted therapies with BRAF and MEK inhibitors showed promising results over the past years, but it is known that most responses are temporary, and almost all of patients develop a tumor relapse within one year. Different drug-resistance mechanisms underlie the progression of disease and activation of both MAPK and PI3K/AKT/mTOR pathways. Therefore, in this article we reviewed the main studies about clinical effects of several target inhibitors, describing properly the most prominent mechanisms of both intrinsic and acquired resistance. Furthermore, suggestive strategies for overcoming drug resistance and the most recent alternative combination therapies to optimize the use of MAPK pathway inhibitors were also discussed.

We compared 2-[fluorine-18] fluoro-2-deoxy- d -glucose PET-CT and contrast-enhanced computed tomography (CECT) in 62 consecutive patients with newly diagnosed Hodgkin Lymphoma (HL), aiming to provide evidences that may spare CECT from the staging procedures of HL patients. Among a total of 1448 nodal sites examined, disease involvement was detected in 232 (16%) and 280 (19.3%) nodal areas by CECT and PET-CT, respectively (P A total of 248 extranodal areas were examined. CECT and PET-CT identified disease involvement in 19 (7.7%) and 25 (10.1%) extranodal areas, respectively (P = n.s). Compared to PET-CT, CECT detected a lower number of cases with bone and/or bone marrow involvement (P = 0.05), whereas no differences were detected at the level of lung. By contrast, CECT identified liver lesions in four patients versus three identified by PET-CT. In comparison to CECT, PET-CT upstaged 6 patients (9.7%) and downstaged 1 patient (1.6%). We showed that PET-CT modified treatment strategy in five (8.1%) cases not only as a result of stage advancement (2 cases) but also of a different prognostic stratification in patients with localized disease (3 cases), due to the better sensitivity in detecting nodal involvement. In conclusion, our data, confirm the superiority of PET-CT in detecting disease involvement at diagnosis of HL, and further supports the possibility to replace CECT with PET-CT in the initial staging of HL.

We compared 2-[fluorine-18] fluoro-2-deoxy-d-glucose PET-CT and contrast-enhanced computed tomography (CECT) in 62 consecutive patients with newly diagnosed Hodgkin Lymphoma (HL), aiming to provide evidences that may spare CECT from the staging procedures of HL patients. Among a total of 1448 nodal sites examined, disease involvement was detected in 232 (16%) and 280 (19.3%) nodal areas by CECT and PET-CT, respectively (P 0.01). Sensitivity of CECT in detecting disease involvement ranged from 0% for internal mammary region (7 cases) and Waldayer's ring (1 case) to 100% for mediastinum. A total of 248 extranodal areas were examined. CECT and PET-CT identified disease involvement in 19 (7.7%) and 25 (10.1%) extranodal areas, respectively (P = n.s). Compared to PET-CT, CECT detected a lower number of cases with bone and/or bone marrow involvement (P = 0.05), whereas no differences were detected at the level of lung. By contrast, CECT identified liver lesions in four patients versus three identified by PET-CT. In comparison to CECT, PET-CT upstaged 6 patients (9.7%) and downstaged 1 patient (1.6%). We showed that PET-CT modified treatment strategy in five (8.1%) cases not only as a result of stage advancement (2 cases) but also of a different prognostic stratification in patients with localized disease (3 cases), due to the better sensitivity in detecting nodal involvement. In conclusion, our data, confirm the superiority of PET-CT in detecting disease involvement at diagnosis of HL, and further supports the possibility to replace CECT with PET-CT in the initial staging of HL.